Efek Pemberian Pravastatin terhadap Ekspresi Imunohistokimia Soluble Fms-like Tyrosine Kinase (sFlt-1) dan Soluble Endoglin (sEng) pada Tikus Model Preeklampsia

Abstract

Latar belakang: Preeklampsia berkaitan dengan peningkatan morbiditas dan mortalitas ibu dan bayi. Secara patogenesis plasentasi yang abnormal diyakini merupakan dasar terjadinya sindroma preeklampsia, dimana peningkatan kadar soluble fms-like tyrosine kinase-1 (sFlt-1) dan soluble endoglin (sEng) pada preeklampsia akan menyebabkan terjadinya disfungsi endotel secara sistemik. Saat ini upaya pencegahan dan terapi preeklampsia sedang dikembangkan menggunakan berbagai macam obat-obatan. Studi invitro terbaru saat ini menunjukan pravasatin potensial menjadi terapi untuk preeklampsia. Pravastatin diyakini memiliki efek pleiotropik sebagai anti-inflamasi, anti-oksidan, anti-trombotik, pro-angiogenik, dan protektif terhadap endothelium Metode: Penelitian ini menggunakan jenis penelitian analitik dengan desain eksperimental murni pada tikus laboratorium (Rattus Norvegicus) betina hamil sebanyak 32 ekor yang dibagi menjadi 4 kelompok yaitu: (1) Kontrol negatif (tanpa intervensi apapun), (2) Kontrol positif (pemberian lipopolysaccharides/LPS agar menjadi tikus model preeklampsia), (3) Intervensi-1 (pemberian Pravastatin pada tikus model preeklampsia), dan (4) Intervensi-2 (pemberian Pravastatin sebelum menjadi tikus model preeklampsia). Selanjutnya, plasenta diambil pada hari ke 18 kehamilan dan dilakukan proses pembuatan preparat untuk menilai ekspresi sFlt-1 dan sEng pada plasenta yang dinilai oleh dokter spesialis Patologi Anatomi. Hasil: Terdapat perbedaan signifikan pada nilai sistolik, diastolik, dan Mean arterial Pressure (MAP) antara keempat kelompok setelah dilakukan intervensi pravastatin (p<0,001). Pada pemeriksaan urinalisis, didapatkan penurunan kualitatif proteinuria setelah dilakukan intervensi pravastatin. Ekspresi IHK sFlt-1 dan sEng pada kelompok kontrol positif lebih tinggi dibandingkan dengan kelompok lain (8±2 dan 9±1). Terdapat perbedaan ekspresi sFlt-1 dan sEng yang signifikan pada setiap kelompok setelah pemberian pravastatin. (p=0,002 dan p<0,001). Kesimpulan: Terdapat perbedaan nilai sistol, diastol, MAP, proteinuria, ekspresi sEng dan sFlt-1 yang signifikan pada setiap kelompok setelah pemberian pravastatin.

Background: Preeclampsia is associated with increased maternal and perinatal morbidity and mortality. Abnormal placentation is believed to be the basis of the preeclampsia syndrome. Where increased levels of Soluble Fms-Like Tyrosine Kinase-1 (sFlt-1) and Soluble Endoglin (sEng) in preeclampsia will cause systemic endothelial dysfunction. Currently, many researchs are being developed using a variety of drugs to prevent and treat preeclampsia. Recent in vitro studies have shown pravasatin potential as a therapy for preeclampsia. Pravastatin is believed to have pleiotropic effects as anti-inflammatory, anti-oxidant, anti-thrombotic, pro-angiogenic, and protective of the endothelium. Based on this description, researchers are interested in investigating the effect of giving pravastatin as a prevention and treatment of preeclampsia by improving blood pressure, proteinuria, sFlt-1 and sEng expression. Methods: This study used an analytic study with a pure experimental design on 32 female pregnant rat laboratory (Rattus Norvegicus) which were divided into 4 groups: (1) Negative control group (without any intervension), (2) Positive control group (administration of lipopolysaccharides/LPS to generate preeclampsia rat model), (3) Intervension-1 group ( Pravastatin administration on preeclampsia rat model), (4) intervension-2 group (Pravastatin administration before become preeclampsia rat model). The placenta was taken on 18 day of pregnancy and Immunohistochemistry (IHC) was performed to assess expression of sFlt-1 and sEng in the placenta which was assessed by a Pathologist. Results: There were significant differences in systolic, diastolic, and Mean Arterial Pressure (MAP) values between the four groups after pravastatin intervention (p<0.001). On urinalysis examination, there was a qualitative decrease in proteinuria after the intervention. The expression of sFlt-1 and sEng in the positive control group was higher than that of the other groups (8±2 and 9±1). There were significant differences in the expression of sFlt-1 and sEng in each group after pravastatin administration. (p=0.002 and p<0.001). Conclusion: There were significant differences in systolic, diastolic, MAP, proteinuria, sEng and sFlt-1 expression in each group after pravastatin administration.